Elastic light scattering from single microparticles on a femtosecond time scale.
Experimentally measured and theoretically calculated elastic light-scattering spectra from single microparticles illuminated by 100-fs pulses are presented. Although in the theoretical calculation only a single incoming femtosecond laser pulse was used, the spectral behavior of scattered light shows all the features seen in the experimental spectrum from many femtosecond pulses, including morphology-dependent resonances (MDR's). The good agreement between experimental and theoretical elastic light-scattering data has stimulated a theoretical investigation of the time-dependent behavior of the elastically scattered light from a single microparticle on a femtosecond time scale. Since the spatial pulse length of the incoming laser pulse is smaller than the particle circumference, the temporal behavior of reflection, diffraction, refraction, and coupling into MDR's can be distinguished. Since the time-dependent scattering is strongly dependent on particle size, refractive index, and pulse chirp, it may be possible to encode several bits of information into a single laser pulse and therefore to increase optical data communication rates.


Governing the Interlinkages between the Sustainable Development Goals: Approaches to Attain Policy Integration.
The Sustainable Development Goals (SDGs) of 2015 form a universal and integrated policy agenda to be realized over the next 15 years. One of the targets is the attainment of policy coherence for sustainable development, which requires the individual goals to become interlinked. This article's main research interest lies in assessing how national governments and their competent ministries interpret and strive to implement the target of policy coherence for sustainable development. Drawing on the Voluntary National Reviews submitted in 2016 and 2017 by six countries, this study shows that at the national level, the links among the different goals and the idea of policy integration are subject to divergent interpretations. The differences observed do not stem from the interlinkages of the SDGs as defined by the United Nations, neither do they result from different levels of income or degree of political centralization. Instead, the respective domestic policy-making processes are likely to explain the implementation strategies adopted by the individual states. For example, the implementation approach adopted by the government of Turkey suggests that path-dependency is critical, whereas the Colombian approach consists of defining new policy measures and institutional arrangements.


Effects of five nights of normobaric hypoxia on the ventilatory responses to acute hypoxia and hypercapnia.
This study examined the effects of five nights of normobaric hypoxia on ventilatory responses to acute isocapnic hypoxia (AHVR) and hyperoxic hypercapnia (AHCVR). Twelve male subjects (26.6 +/- 4.1 years, standard deviation (S.D.)) slept 8-9 h per day overnight for 5 consecutive days at a simulated altitude of 4,300 m (FiO2= approximately 13.8%). Using the technique of dynamic end-tidal forcing, the AHVR and AHCVR were assessed twice prior to, immediately after, and 5 days following the hypoxic exposure. Immediately following the exposure, AHVR was increased by 1.6 +/- 1.3 L min(-1) %(-1) (P<0.01) when compared with control values. Likewise, after the exposure, ventilation in hyperoxia was increased (P<0.001) and was associated with both an increase in the slope (1.5 +/- 1.4 L min(-1) Torr(-1); P<0.05) and decrease in the intercept (-2.7 +/- 4.3 Torr; P<0.05) of the AHCVR. These results show that five nights of hypoxia can elicit similar perturbations, in both AHVR and AHCVR, as have been reported during more chronic altitude exposures.


In vivo verification of superficial dose for head and neck treatments using intensity-modulated techniques.
Skin dose is one of the key issues for clinical dosimetry in radiation therapy. Currently planning computer systems are unable to accurately predict dose in the buildup region, leaving ambiguity as to the dose levels actually received by the patient's skin during radiotherapy. This is one of the prime reasons why in vivo measurements are necessary to estimate the dose in the buildup region. A newly developed metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector designed specifically for dose measurements in rapidly changing dose gradients was introduced for accurate in vivo skin dosimetry. The feasibility of this detector for skin dose measurements was verified in comparison with plane parallel ionization chamber and radiochromic films. The accuracy of a commercial treatment planning system (TPS) in skin dose calculations for intensity-modulated radiation therapy treatment of nasopharyngeal carcinoma was evaluated using MOSFET detectors in an anthropomorphic phantom as well as on the patients. Results show that this newly developed MOSFET detector can provide a minimal but highly reproducible intrinsic buildup of 7 mg cm(-2) corresponding to the requirements of personal surface dose equivalent Hp (0.07). The reproducibility of the MOSFET response, in high sensitivity mode, is found to be better than 2% at the phantom surface for the doses normally delivered to the patients. The MOSFET detector agrees well with the Attix chamber and the EBT Gafchromic film in terms of surface and buildup region dose measurements, even for oblique incident beams. While the dose difference between MOSFET measurements and TPS calculations is within measurement uncertainty for the depths equal to or greater than 0.5 cm, an overestimation of up to 8.5% was found for the surface dose calculations in the anthropomorphic phantom study. In vivo skin dose measurements reveal that the dose difference between the MOSFET results and the TPS calculations was on average -7.2%, ranging from -4.3% to -9.2%. The newly designed MOSFET detector encapsulated into a thin water protective film has a minimal reproducible intrinsic buildup recommended for skin dosimetry. This feature makes it very suitable for routine IMRT QA and accurate in vivo skin dosimetry.


Semi-Individualized Homeopathy Add-On Versus Usual Care Only for Premenstrual Disorders: A Randomized, Controlled Feasibility Study.
Premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD) bother a substantial number of women. Homeopathy seems a promising treatment, but it needs investigation using reliable study designs. The feasibility of organizing an international randomized pragmatic trial on a homeopathic add-on treatment (usual care [UC] + HT) compared with UC alone was evaluated. A multicenter, randomized, controlled pragmatic trial with parallel groups. The study was organized in general and private homeopathic practices in the Netherlands and Sweden and in an outpatient university clinic in Germany. Women diagnosed as having PMS/PMDD, based on prospective daily rating by the daily record of severity of problems (DRSP) during a period of 2 months, were included and randomized. Women were to receive UC + HT or UC for 4 months. Homeopathic medicine selection was according to a previously tested prognostic questionnaire and electronic algorithm. Usual care was as provided by the women's general practitioner according to their preferences. Before and after treatment, the women completed diaries (DRSP), the measure yourself concerns and well-being, and other questionnaires. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. In Germany, the study could not proceed because of legal limitations. In Sweden, recruitment proved extremely difficult. In the Netherlands and Sweden, 60 women were randomized (UC + HT: 28; UC: 32), data of 47/46 women were analyzed (ITT/PP). After 4 months, relative mean change of DRSP scores in the UC + HT group was significantly better than in the UC group (p = 0.03). With respect to recruitment and different legal status, it does not seem feasible to perform a larger, international, pragmatic randomized trial on (semi-)individualized homeopathy for PMS/PMDD. Since the added value of HT compared with UC was demonstrated by significant differences in symptom score changes, further studies are warranted.


Orthogonal aberration functions for high-aperture optical systems.
Aberration functions that are a complete, orthogonal, and normalized set over a weighted spherical pupil are developed. A general weighting is considered, for which special cases are applicable to systems satisfying the Abbe sine condition and the Herschel condition. Paraboloidal mirrors are also considered. This weighting can also be used to account empirically for Fresnel reflection losses in the optical system. The functions can be expressed in an analytic form. Expressions are given for 24 low-order aberrations.


Development and Implementation of the DHAPP Military eHealth Information Network System.
As the Joint United Nations Programme on HIV/AIDS, the Global Fund, and the US President's Emergency Plan for AIDS Relief focus on reaching 90-90-90 goals, military health systems are scaling up to meet the data demands of these ambitious objectives. Since 2008, the US Department of Defense HIV/AIDS Prevention Program (DHAPP) has been working with military partners in 14 countries on implementation and adoption of a Military eHealth Information Network (MeHIN). Each country implementation plan followed a structured process using international eHealth standards. DHAPP worked with the private sector to develop a commercial-off-the-shelf (COTS) electronic medical record (EMR) for the collection of data, including patient demographic information, clinical notes for general medical care, HIV encounters, voluntary medical male circumcision, and tuberculosis screening information. The COTS software approach provided a zero-dollar software license and focused on sharing a single version of the EMR across countries, so that all countries could benefit from software enhancements and new features over time. DHAPP also worked with the public sector to modify open source disease surveillance tools and open access of HIV training materials. Important lessons highlight challenges to eHealth implementation, including a paucity of technology infrastructure, military leadership rotations, and the need for basic computer skills building. While not simple, eHealth systems can be built and maintained with requisite security, flexibility, and reporting capabilities that provide critical information to improve the health of individuals and organizations.


Crebbp haploinsufficiency in mice alters the bone marrow microenvironment, leading to loss of stem cells and excessive myelopoiesis.
CREB-binding protein (CREBBP) is important for the cell-autonomous regulation of hematopoiesis, including the stem cell compartment. In the present study, we show that CREBBP plays an equally pivotal role in microenvironment-mediated regulation of hematopoiesis. We found that the BM microenvironment of Crebbp(+/-) mice was unable to properly maintain the immature stem cell and progenitor cell pools. Instead, it stimulates myeloid differentiation, which progresses into a myeloproliferation phenotype. Alterations in the BM microenvironment resulting from haploinsufficiency of Crebbp included a marked decrease in trabecular bone that was predominantly caused by increased osteoclastogenesis. Although CFU-fibroblast (CFU-F) and total osteoblast numbers were decreased, the bone formation rate was similar to that found in wild-type mice. At the molecular level, we found that the known hematopoietic modulators matrix metallopeptidase-9 (MMP9) and kit ligand (KITL) were decreased with heterozygous levels of Crebbp. Lastly, potentially important regulatory proteins, endothelial cell adhesion molecule 1 (ESAM1) and cadherin 5 (CDH5), were increased on Crebbp(+/-) endothelial cells. Our findings reveal that a full dose of Crebbp is essential in the BM microenvironment to maintain proper hematopoiesis and to prevent excessive myeloproliferation.


Experimental investigation of the intensity fluctuation joint probability and conditional distributions of the twin-beam quantum state.
We give the intensity fluctuation joint probability of the twin-beam quantum state, which was generated with an optical parametric oscillator operating above threshold. Then we present what to our knowledge is the first measurement of the intensity fluctuation conditional probability distributions of twin beams. The measured inference variance of twin beams 0.62+/-0.02, which is less than the standard quantum limit of unity, indicates inference with a precision better than that of separable states. The measured photocurrent variance exhibits a quantum correlation of as much as -4.9+/-0.2 dB between the signal and the idler.


Mortality in psychotic depression: 18-year follow-up study.
Evidence on the role of co-occurring psychiatric disorders in mortality associated with psychotic depression is limited. To estimate the risk of cause-specific mortality in psychotic depression compared with severe non-psychotic depression while controlling for comorbid psychiatric disorders. This cohort study used routine data from nationwide health registers in Finland. Eligible participants had their first diagnosis for psychotic depression or for severe non-psychotic depression between the years 2000 and 2018, had no pre-existing diagnoses for schizophrenia spectrum disorders or bipolar disorder, and were aged 18-65 years at the index diagnosis. Causes of death were defined by ICD-10 codes. The follow-up time was up to 18 years. We included 19 064 individuals with incident psychotic depression and 90 877 individuals with incident non-psychotic depression. Half (1199/2188) of the deaths in those with psychotic depression occurred within 5 years from the index diagnosis and the highest relative risk was during the first year after the diagnosis. Compared with individuals with non-psychotic depression, those with psychotic depression had a higher risk of all-cause mortality (adjusted hazard ratio, aHR = 1.59, 95% CI 1.48-1.70), suicides (aHR = 2.36, 95% CI 2.11-2.64) and fatal accidents (aHR 1.63, 95% CI 1.26-2.10) during the subsequent 5-year period after the index diagnosis. Psychotic symptoms markedly added to the mortality risk associated with severe depression after controlling for psychiatric comorbidity. Prompt treatment and enhanced monitoring for psychotic symptoms is warranted in all patients with severe depression to prevent deaths because of suicides and other external causes.


The Oncology Nursing Society Leadership Competency project: developing a road map to professional excellence.
Combining the recommendations of the Institute of Medicine's report on the future of nursing, an Oncology Nursing Society (ONS) leadership think tank, and current evidence, the ONS Leadership Competencies were developed to provide all nurses with a pathway to advance their leadership skills and abilities. Generated through a systematic approach of literature review, data synthesis, and peer and expert review, the ONS Leadership Competencies are divided into five domains: vision, knowledge, interpersonal effectiveness, systems thinking, and personal mastery. Each of the competencies can be measured at the individual, group, and governance levels. They serve as a means of self-assessment, growth, future planning, and professional development. This article describes the process used to develop the ONS Leadership Competencies and offers examples of how they may be used in practice.


Transformation of 2,4,6-trichlorophenol by the white rot fungi Panus tigrinus and Coriolus versicolor.
The toxicity of thirteen isomers of mono-, di-, tri- and pentachlorophenols was tested in potato-dextrose agar cultures of the white rot fungi Panus tigrinus and Coriolus versicolor. 2,4,6-Trichlorophenol (2,4,6-TCP) was chosen for further study of its toxicity and transformation in liquid cultures of these fungi. Two schemes of 2,4,6-TCP addition were tested to minimize its toxic effect to fungal cultures: stepwise addition from the moment of inoculation and single addition after five days of growth. In both cases the ligninolytic enzyme systems of both fungi were found to be responsible for 2,4,6-TCP transformation. 2,6-Dichloro-1,4-hydroquinol and 2,6-dichloro-1,4-benzoquinone were found as products of primary oxidation of 2,4,6-TCP by intact fungal cultures and purified ligninolytic enzymes, Mn-peroxidases and laccases of both fungi. However, primary attack of 2,4,6-TCP in P. tigrinus culture was conducted mainly by Mn-peroxidase, while in C. versicolor it was catalyzed predominantly by laccase, suggesting a different mode of regulation of these enzymes in the two fungi.


Analysis of tetrahydroxylated benzo[a]pyrene isomers in hair as biomarkers of exposure to benzo[a]pyrene.
A first gas chromatography-tandem mass spectrometry (GC-MS/MS) method was designed for analysis of four tetrahydroxylated benzo[a]pyrene metabolites (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol) in hair. Hair powder extract was submitted to liquid-solid extraction, followed by C18 solid-phase purification. The analytes were derivatized with use of N-methyl-N-(trimethylsilyl)trifluoroacetamide and then analyzed by GC-MS/MS in negative chemical ionization mode. The calibration curve was linear from the limit of quantification (LOQ) to 20 pg/mg in hair. The coefficient of determination of the calibration curve was more than 0.975 for all the analytes investigated. The LOQs ranged from 0.075 to 0.2 pg/mg in hair. The method was afterward applied to the analysis of hair of 16 rats randomly allocated to experimental groups receiving 16 polycyclic aromatic hydrocarbons solubilized in oil at 0 or 0.8 mg/kg body weight by oral administration three times per week for 90 days. The analysis of monohydroxylated and dihydroxylated benzo[a]pyrenes was conducted in parallel by GC-MS/MS on the same samples. All tetrahydroxylated benzo[a]pyrene isomers were detected in hair samples collected from rats exposed to polycyclic aromatic hydrocarbons. Benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, the most abundant isomer in hair of treated rats, was also the principal isomer released in DNA adduct hydrolysis in humans. Moreover, the benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol concentrations in hair were significantly greater than those of 2-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, 7-hydroxybenzo[a]pyrene, and 4-hydroxybenzo[a]pyrene and similar to those of 9-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. The method was also sufficiently sensitive to monitor environmental levels of exposure because two hair specimens in the eight analyzed from smokers were above the LOQ for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol. This study therefore demonstrated that tetrahydroxylated benzo[a]pyrenes in hair might be a useful biomarker for the assessment of both the general population and occupationally exposed workers.


In situ X-ray probing reveals fingerprints of surface platinum oxide.
In situ X-ray absorption spectroscopy (XAS) at the Pt L(3) edge is a useful probe for Pt-O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard X-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF code and complementary extended X-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at high electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.


[The use of anticonvulsants and the levels of folate, vitamin B12 and homocysteine].
BACKGROUND Patients with epilepsy who use anticonvulsants frequently show low levels of folate and vitamin B12 and high levels of homocysteine. Patients with bipolar disorder use some anticonvulsants as mood stabilisers.
 AIM: To determine whether some anticonvulsants lower folate and vitamin B12 and raise homocysteine levels.
 METHOD: Systematic literature search to determine the relation between the anticonvulsants valproic acid, carbamazepine, lamotrigine and topiramate on the one hand and blood levels of folate, vitamin B12 and homocysteine on the other hand.
 RESULTS: The vast majority of studies in adults and children showed a correlation between use of anticonvulsant carbamazepine and decrease of the folate level. Hardly any of the studies that examined the effect of valproic acid on folate levels found a correlation. There was next to no evidence of a correlation between the use of carbamazepine and a low vitamin B12 level in adults or children. In adults and children the use of valproic acid was found to correlate with a higher vitamin B12 level. Nearly all studies found an increase in homocysteine in adults and children using carbamazepine. Among the users of valproic acid, it was only children who showed a clear association with a rise in homocysteine level. The results for adults were contradictory. We were unable to make any clear statement about topiramate or lamotrigine because there have been very few publications about these anticonvulsants.
 CONCLUSION: In adults and children with epilepsy use of carbamazepine is associated with a decrease of folate, valproic acid with a rise in the vitamin B12 level, and carbamazepine with an increase in homocysteine. Valproic acid showed only in children an association with the rise of the homocysteine level. Psychiatrists may find it advisable to control the levels of folate and homocysteine in adults and children who are taking carbamazepine and to measure homocysteine level in children taking valproic acid.


Photocatalytic H2 evolution on MoS2-TiO2 catalysts synthesized via mechanochemistry.
At present, composite photocatalysts containing MoS2 as a co-catalyst and a subjective semiconductor material are usually obtained via various complex reduction methods using NH4MoS4 or Na2MoO4 as a precursor. In this work, a simple method was proposed to synthesize MoS2-TiO2 composite photocatalysts via mechanochemistry using MoS2 as a direct precursor. 4.0% MoS2-TiO2 after ball-milling at 300 rpm for 2 h possessed the maximum photocatalytic activity for H2 evolution. The rate of H2 evolution was up to 150.7 μmol h(-1), which was 48.6 times higher than that of pure TiO2. The MoS2-TiO2 composite possesses stable photocatalytic performance for H2 evolution. Photoelectrochemical measurements confirmed the electronic interaction between TiO2 and MoS2. The photo-generated electrons on the conduction band of TiO2 could easily transfer to the MoS2 co-catalyst, which promoted efficient charge separation and improved the photocatalytic performance.


Incidence and Determinants of Complications in Rotational Atherectomy: Insights From the National Clinical Data (J-PCI Registry).
The usage of rotational atherectomy (RA) is growing in the current percutaneous coronary intervention (PCI) because of the expansion of PCI indication to more complex lesions. However, the complications after RA have been linked to procedure-related morbidity and mortality. The purpose of this study was to investigate the incidence and determinants of complications in RA using a large nationwide registration system in Japan (J-PCI). The primary composite outcome of this study was defined as the occurrence of in-hospital death, cardiac tamponade, and emergent surgery after RA. A total of 13 335 RA cases (3.2% of registered PCI cases) were analyzed. The composite outcome was observed in 175 cases (1.31%) and included 80 in-hospital deaths (0.60%), 86 tamponades (0.64%), and 24 emergent surgeries (0.18%). The clinical variables associated with occurrence of the composite outcome were age (odds ratio [OR] 1.03 per unit increment, 95% confidence interval [CI] 1.02-1.05), impaired kidney function (OR 1.59, 95% CI 1.15-2.19), previous myocardial infarction (OR 1.69, 95% CI 1.21-2.35), emergent PCI (OR 4.02, 95% CI 1.66-8.27), and triple-vessel disease (versus single-vessel disease: OR 2.17, 95% CI 1.43-3.28). Notably, institutional volume of RA cases was inversely associated with the composite outcomes (high- versus low-volume institution: OR 0.56, 95% CI 0.36-0.89). The reported incidence of important procedure-related complication rate was 1.3%, with each component ranging between 0.2% and 0.6% in J-PCI. Its determinants were both patient related (age, impaired kidney function, and previous myocardial infarction) and procedure related (emergent procedures, number of diseased vessels, and institutional volume of RA).


Diarylheptanoids derived from Alpinia officinarum induce apoptosis, S-phase arrest and differentiation in human neuroblastoma cells.
We have previously screened many natural products for their cytotoxic effects on neuroblastoma cell lines, and two diarylheptanoids derived from Alpinia officinarum, 7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one (Compound 1) and (5R)-5-methoxy-7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-3-heptanone (Compound 2), were shown to have potent cytotoxicity. On this basis, a detailed study of the antitumor activities of these two diarylheptanoids in neuroblastoma cell lines was performed. Cytotoxicity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. To measure apoptosis, nuclear shrinkage was monitored by Hoechst 33342 staining, and activation of caspases 3 and 9 was monitored by Western blotting. Cell cycle status was evaluated by flow cytometry with propidium iodide staining. Differentiated cells were photographed and counted in a randomized fashion. Both diarylheptanoids showed significant cytotoxicity against neuroblastoma cell lines (IMR-32, SK-N-SH, NB-39). The compounds induced nuclear shrinkage and fragmentation, and activated caspase-3 and caspase-9. Flow cytometric analysis revealed induction of S-phase cell cycle arrest concurrently with an increased sub-G(1) cell population. Moreover, a low concentration (10(-8) M) of Compound 1 induced significant neurite branching in the NB-39 cell line. Diarylheptanoids derived from A. officinarum have marked activity against neuroblastoma cells, acting through multiple mechanisms. Our results suggest that the two compounds studied here may be useful for the treatment of patients with neuroblastoma.


Validation and reliability analysis of the Portuguese language version of Needs of Parents Questionnaire.
To describe the procedures followed for the validation and reliability analysis of the Portuguese version of the Needs of Parents Questionnaire in the context of pediatric hospitalization in Portugal. This is a descriptive study based on procedures for the cultural and linguistic adaptation of health measurement tools. The validation was performed on a sample of 870 parents of hospitalized children in pediatrics departments from four hospitals in Portugal, with ages ranging from 2 days to 18 years. Content validity was assured by two cognitive debriefing meetings, separately organized with parents and staff. The reliability of the Portuguese version was assessed through reproducibility tests and internal consistency computation. Using Cronbach's alpha, results from the cognitive debriefing and internal consistency scores were similar to those obtained by the authors of the original version and good for the three subscales, allowing us to state that the questionnaire has the adequate psychometric properties to measure parents' needs. It was well accepted by parents, who valued all needs, especially the need to trust the care provided to their child when they are not present, as well as the need to be trusted and the need for information. The questionnaire proved to be a valid and reliable measurement instrument to assess the needs of parents during their pediatric hospitalizations. The Portuguese version of the Needs of Parents Questionnaire has been validated.


Computational replication of the patient-specific stenting procedure for coronary artery bifurcations: From OCT and CT imaging to structural and hemodynamics analyses.
The optimal stenting technique for coronary artery bifurcations is still debated. With additional advances computational simulations can soon be used to compare stent designs or strategies based on verified structural and hemodynamics results in order to identify the optimal solution for each individual's anatomy. In this study, patient-specific simulations of stent deployment were performed for 2 cases to replicate the complete procedure conducted by interventional cardiologists. Subsequent computational fluid dynamics (CFD) analyses were conducted to quantify hemodynamic quantities linked to restenosis. Patient-specific pre-operative models of coronary bifurcations were reconstructed from CT angiography and optical coherence tomography (OCT). Plaque location and composition were estimated from OCT and assigned to models, and structural simulations were performed in Abaqus. Artery geometries after virtual stent expansion of Xience Prime or Nobori stents created in SolidWorks were compared to post-operative geometry from OCT and CT before being extracted and used for CFD simulations in SimVascular. Inflow boundary conditions based on body surface area, and downstream vascular resistances and capacitances were applied at branches to mimic physiology. Artery geometries obtained after virtual expansion were in good agreement with those reconstructed from patient images. Quantitative comparison of the distance between reconstructed and post-stent geometries revealed a maximum difference in area of 20.4%. Adverse indices of wall shear stress were more pronounced for thicker Nobori stents in both patients. These findings verify structural analyses of stent expansion, introduce a workflow to combine software packages for solid and fluid mechanics analysis, and underscore important stent design features from prior idealized studies. The proposed approach may ultimately be useful in determining an optimal choice of stent and position for each patient.


Symmetrical Drug-related Intertriginous and Flexural Exanthema (Baboon Syndrome).
Baboon syndrome, also called symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), is an erythematous maculopapular rash that presents in skin folds in a symmetrical pattern. This condition may develop after the patient starts a particular agent. Treatment consists of stopping the associated trigger and medicating with topical or systemic corticosteroids. A 30-year-old man with odynophagia, otalgia and fever was prescribed amoxicillin. He developed erythematous and pruriginous lesions in the cubital fossa and inguinal regions. He attended the emergency department (ED) where he was prescribed penicillin. Lesions continued to progressively worsen with a bilateral symmetrical pattern in the axillary region and later in the nape folds, popliteal regions, and on the perineum and buttocks. The patient presented to the ED for a second time, where he was diagnosed with baboon syndrome and prescribed topical steroids with clear improvement. It is important to identify adverse drug effects.Baboon syndrome is rare and secondary to the use of particular drugs.The diagnosis is based mainly on the patient's clinical presentation.


ATP13A2/PARK9 regulates secretion of exosomes and α-synuclein.
Kufor-Rakeb syndrome (KRS) is caused by loss-of-function mutations in ATP13A2 (PARK9) and characterized by juvenile-onset parkinsonism, pyramidal signs, and cognitive decline. Previous studies suggested that PARK9 deficiency causes lysosomal dysfunction and α-synuclein (α-syn) accumulation, whereas PARK9 overexpression suppresses toxicity of α-syn. However, the precise mechanism of PARK9 effect on lysosomes and α-syn has been unknown. Here, we found that overexpressed PARK9 localized to multivesicular bodies (MVBs) in the human H4 cell line. The results from patient fibroblasts showed that loss of PARK9 function leads to decreased number of the intraluminal vesicles in MVBs and diminished release of exosomes into culture media. By contrast, overexpression of PARK9 results in increased release of exosomes in H4 cells and mouse primary cortical neurons. Moreover, loss of PARK9 function resulted in decreased secretion of α-syn into extracellular space, whereas overexpressed PARK9 promotes secretion of α-syn, at least in part via exosomes. Finally, we found that PARK9 regulates exosome biogenesis through functional interaction with the endosomal sorting complex required for transport machinery. Together, these data suggest the involvement of PARK9 in the biogenesis of exosomes and α-syn secretion and raise a possibility that disruption of these pathways in patients with KRS contributes to the disease pathogenesis.


Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions.
A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.


Connectivity measures in the Poffenberger paradigm indicate hemispheric asymmetries.
The Poffenberger paradigm is a well-known measure of interhemispheric transfer delays, calculated on the basis of the crossed vs uncrossed reaction time difference (CUD). However, the proper interpretation of CUD is extensively debated in the literature. In this study we used connectivity measures in an attempt to interpret CUD from the perspective of functional connectivity. Accordingly, we tried to define functional couplings in the Poffenberger paradigm; we used a simple choice version of the paradigm, and included a stimulation only (SO) condition for comparison. As an index of functional coupling we employed partial directed coherence, exploiting bilateral grouping of the electrodes to compute intra-and interhemispheric connection weight ratios (CWRs). Our findings indicated modulations in functional weights in relation to the SO condition, rather than the crossed and uncrossed conditions, such that the response executed by the right hemisphere yielded a decrease in intra-, yet an increase in interhemispheric CWRs, whereas the left hemisphere interactions showed connectivity patterns similar to the SO condition irrespective of the side of movement. Overall, our results suggest modulation of connectivity in the same/similar system, which was found to be optimized, in terms of hemispheric asymmetries, to different tasks.


Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice.
The endocannabinoid system is involved in the regulation of gastrointestinal (GI) motility and inflammation. Using the peripherally restricted cannabinoid (CB)(1)/CB(2) receptor agonist naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), we investigated the role of peripheral cannabinoid receptors in the regulation of GI motility and the development of colitis in mice. The actions of SAB378 on whole gut transit, upper GI transit, colonic propulsion, and locomotor activity were investigated in C57BL/6N, CB(1) receptor knockout, and CB(2) receptor knockout mice. The potential for SAB378 to modify inflammation was studied by using dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) models of experimental colitis. SAB378 did not modify locomotor activity. SAB378 slowed all parameters of GI motility, and these effects were significantly reduced by the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM251), but not by the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H- indol-3-yl](4-methoxyphenyl)methanone (AM630). SAB378 did not inhibit GI transit or colonic propulsion in CB(1) receptor knockout mice, whereas its effects were observed in CB(2) receptor knockout mice. SAB378 did not reduce the degree of colitis induced by DSS or TNBS. The actions of SAB378 on GI motility are mediated by peripherally located CB(1) receptors. SAB378 was not effective against two models of experimental colitis, which may indicate that peripheral cannabinoid receptor stimulation alone may not be sufficient to mediate the anti-inflammatory effects of cannabinoids.


A Novel Technique for Fetal ECG Extraction Using Single-Channel Abdominal Recording.
Non-invasive fetal electrocardiograms (FECGs) are an alternative method to standard means of fetal monitoring which permit long-term continual monitoring. However, in abdominal recording, the FECG amplitude is weak in the temporal domain and overlaps with the maternal electrocardiogram (MECG) in the spectral domain. Research in the area of non-invasive separations of FECG from abdominal electrocardiograms (AECGs) is in its infancy and several studies are currently focusing on this area. An adaptive noise canceller (ANC) is commonly used for cancelling interference in cases where the reference signal only correlates with an interference signal, and not with a signal of interest. However, results from some existing studies suggest that propagation of electrocardiogram (ECG) signals from the maternal heart to the abdomen is nonlinear, hence the adaptive filter approach may fail if the thoracic and abdominal MECG lack strict waveform similarity. In this study, singular value decomposition (SVD) and smooth window (SW) techniques are combined to build a reference signal in an ANC. This is to avoid the limitation that thoracic MECGs recorded separately must be similar to abdominal MECGs in waveform. Validation of the proposed method with r01 and r07 signals from a public dataset, and a self-recorded private dataset showed that the proposed method achieved F1 scores of 99.61%, 99.28% and 98.58%, respectively for the detection of fetal QRS. Compared with four other single-channel methods, the proposed method also achieved higher accuracy values of 99.22%, 98.57% and 97.21%, respectively. The findings from this study suggest that the proposed method could potentially aid accurate extraction of FECG from MECG recordings in both clinical and commercial applications.


New treatments for bacterial keratitis.
Purpose. To review the newer treatments for bacterial keratitis. Data Sources. PubMed literature search up to April 2012. Study Selection. Key words used for literature search: "infectious keratitis", "microbial keratitis", "infective keratitis", "new treatments for infectious keratitis", "fourth generation fluoroquinolones", "moxifloxacin", "gatifloxacin", "collagen cross-linking", and "photodynamic therapy". Data Extraction. Over 2400 articles were retrieved. Large scale studies or publications at more recent dates were selected. Data Synthesis. Broad spectrum antibiotics have been the main stay of treatment for bacterial keratitis but with the emergence of bacterial resistance; there is a need for newer antimicrobial agents and treatment methods. Fourth-generation fluoroquinolones and corneal collagen cross-linking are amongst the new treatments. In vitro studies and prospective clinical trials have shown that fourth-generation fluoroquinolones are better than the older generation fluoroquinolones and are as potent as combined fortified antibiotics against common pathogens that cause bacterial keratitis. Collagen cross-linking was shown to improve healing of infectious corneal ulcer in treatment-resistant cases or as an adjunct to antibiotics treatment. Conclusion. Fourth-generation fluoroquinolones are good alternatives to standard treatment of bacterial keratitis using combined fortified topical antibiotics. Collagen cross-linking may be considered in treatment-resistant infectious keratitis or as an adjunct to antibiotics therapy.


Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1alphaOHase-deficient mice.
Intake of a low-phosphate diet stimulates transepithelial transport of Pi in small intestine as well as in renal proximal tubules. In both organs, this is paralleled by a change in the abundance of the apically localized NaPi cotransporters NaPi type IIa (NaPi-IIa) and NaPi type IIb (NaPi-IIb), respectively. Low-Pi diet, via stimulation of the activity of the renal 25-hydroxyvitamin-D3-1alpha-hydroxylase (1alphaOHase), leads to an increase in the level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D]. Regulation of the intestinal absorption of Pi and the abundance of NaPi-IIb by 1,25(OH)2D has been supposed to involve the vitamin D receptor (VDR). In this study, we investigated the adaptation to a low-Pi diet of NaPi-IIb in small intestine as well as NaPi-IIa in kidneys of either VDR- or 1alphaOHase-deficient mice. In both mouse models, upregulation by a low-Pi diet of the NaPi cotransporters NaPi-IIa and NaPi-IIb was normal, i.e., similar to that observed in the wild types. Also, in small intestines of VDR- and 1alphaOHase-deficient mice, the same changes in NaPi-IIb mRNA found in wild-type mice were observed. On the basis of the results, we conclude that the regulation of NaPi cotransport in small intestine (via NaPi-IIb) and kidney (via NaPi-IIa) by low dietary intake of Pi cannot be explained by the 1,25(OH)2D-VDR axis.


Pattern of presentation of oral health conditions by children at University of Nigeria Teaching Hospital, Enugu: a retrospective study.
The study aimed to determine the pattern of occurrence of oral conditions among children that attended the Child Dental Health clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu over a 45 months period. Clinical records of 305 patients, aged 3 days to 16 years, who attended the Child Dental Health Clinic of the UNTH from April 2008 to December 2011 were retrieved and analyzed. Out of a total of 305 children who visited the Child Dental Health Clinic within this period, there were 148 (48.5%) males and 157 (51.5%) females. The ages ranged from 3 days to 16 years with a mean age of 9.05 years, only 4.6% made asymptomatic visit while 95.4% made symptomatic visit. 68.2% had caries and its sequeale, with no significant difference across the gender ( P = 1.472). Nearly 91.1% had periodontal diseases, with a significant difference noted ( P = 0.020) 2% had tooth developmental anomalies, 10.5% had traumatic dental injuries, 12.1% had malocclusion and other esthetic problems, 15.1% had other oral pathologies, 14.4% had abnormalities of tooth eruption. A significant 95.4% of the children made symptomatic visit. Periodontal disease was the most prevalent finding followed by dental caries. There is an urgent need to increase dental health awareness among children through school based continuing dental education program and also among other pediatric care givers such as parents, teachers, and pediatricians.


Can the feeling scale be used to regulate exercise intensity?
It is important that individuals experience a positive affective response during exercise to encourage future behavior. Exercise intensity is a determinant of the affective response. Current research protocols have failed to find the intensity at which all individuals will experience this positive affective response. Consequently, the purpose of this study was to evaluate whether sedentary women could self-regulate their exercise intensity during exercise using the Hardy and Rejeski Feeling Scale (FS) to experience a specific positive affective state and to examine the specific intensities chosen and their consistency over exercise bouts. Seventeen sedentary women completed eight 30-min laboratory-based treadmill exercise sessions (two sessions were completed each week). In four consecutive sessions, participants exercised at an intensity they perceived corresponded to an FS value of 1 (fairly good) and the other four sessions at an intensity corresponding to an FS value of 3 (good). Measures of exercise intensity were recorded. Participants exercised at a lower intensity to achieve an affective state of good (FS 3) compared with fairly good (FS 1). Both these intensities lay close to the individual's ventilatory threshold. The selected intensity was consistent across trials with intensity increasing across time to maintain the required affective state. Sedentary women can regulate intensity using the FS to experience a pleasant affective state, and the intensities chosen are physiologically beneficial for health and fitness.


Cancer-related fatigue in post-treatment cancer survivors: application of the common sense model of illness representations.
Cancer-related fatigue (CrF) is a common and disruptive symptom that may be experienced during and after cancer. Research into the subjective experience of fatigue in this group is required. The common sense model of self-regulation of health and illness (SRM) addresses personal beliefs or mental representations-whether medically sound or unsubstantiated- that a person holds about a health issue. The current study assesses if the SRM could be used as a theoretical framework for organizing the experiences of people with CrF, with a view to identifying methods to address fatigue in cancer survivors. Four focus groups were held with a total of 18 cancer survivors who reported they experienced 'significant fatigue or reduced energy.' A thematic analysis was conducted within the framework of the SRM. Findings were aligned with the SRM, with participants discussing fatigue with reference to representation, coping, and appraisal of symptoms. In particular, the wider social context of CrF was frequently addressed. Perceived inadequacies in support available to those with lingering fatigue after the completion of cancer treatment were highlighted by the participants. This study explored the subjective experience of fatigue after cancer using the SRM. CrF should be approached as a complex psychosocial issue and considered from the patient perspective to facilitate better understanding and management of symptoms. The SRM is an applicable framework for identifying modifiable factors that could lead to improved coping with CrF in post-treatment cancer survivors.


Relationship between changes in seromucoid concentrations and the rate of oxidation or acetylation of several substrates.
This study was carried out to assess the relationship between turpentine-induced elevation of seromucoids and drug metabolism. Six groups of rats were used; one of them received 1 ml of turpentine sc, another received 1 ml of turpentine by gavage (po), and a third group received, ip, 80 mg/kg of phenobarbital daily for 3 days. Three control groups received saline instead of turpentine. Forty-eight hr later, the serum seromucoids were assayed and the rates of N-demethylation of aminopyrine, O-dealkylation of 7-ethoxycoumarin, and hydroxylation of aniline and total cytochrome were determined in liver microsomes. When turpentine was administered sc, seromucoids increased from 3.15 +/- 0.18 to 16.13 +/- 0.84 g/dl (mean +/- SE) (p less than 0.01), but the rates of N-demethylation (p less than 0.01), of O-dealkylation (p less than 0.01) and of hydroxylation (p less than 0.05) were all decreased. In the rats receiving turpentine po, seromucoids remained unchanged, but the rates of N-demethylation and O-dealkylation as well as the concentration of total cytochrome increased (p less than 0.01). Phenobarbital enhanced significantly the rates of N-demethylation, O-dealkylation, and hydroxylation and the total concentration of cytochrome, without modifying the concentration of seromucoids. In another set of experiments we assessed whether turpentine-induced inflammation would affect the in vivo rate of acetylation of sulfamethazine; the results show that inflammation does not affect the rate of acetylation, despite an important increase in seromucoids. It is concluded that, under the present experimental conditions, there is no direct relationship between changes in seromucoids and the rate of drug metabolism.


Interfacial behavior of benzoic acid and phenylphosphonic acid on nanocrystalline TiO(2) surfaces.
The interfacial behavior of self-assembled thin films of benzoic acid (BA) and phenylphosphonic acid (PPOA) anchored on TiO(2) surfaces was studied by using temperature-dependent diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. On the basis of the disappearance of the OH band from the infrared spectra at room temperature, BA and PPOA appear to adsorb onto TiO(2) surfaces through carboxylate and phosphonate groups, respectively. Above 420 degrees C, DRIFT spectra indicated that both BA and PPOA desorb from TiO(2) surfaces; however, dissimilar desorption behavior could be inferred for BA and PPOA from their temperature-dependent spectral changes. The benzene ring modes of PPOA remained above 420 degrees C, whereas those of BA disappeared. Density functional theory calculations showed that the adsorption of BA and PPOA on TiO(2) surfaces corresponded to bidentate bridging geometry on TiO(2) surfaces, and the adsorption of PPOA is stronger than that of BA. The monodentate structures with energy differences of 4.9 and 9.1 kcal mol(-1) from the most stable bidentate structures of BA and PPOA, respectively, from the DFT calculations appeared to be possible, particularly at the high temperatures above 420 degrees C, as indicated by the intensified OH bands. The geometry of PPOA was also estimated to be more upright standing than that of BA on TiO(2) surfaces, which may lead a rather straight detachment from the TiO(2) surfaces based on the presence of in-plane ring modes in the DRIFT spectra at the higher temperature.


Sodium-lithium countertransport and probability of hypertension in Caucasians 47 to 89 years old.
The objectives of the present study were to determine whether sodium-lithium countertransport contributes to predicting the probability of having hypertension and to determine whether it does so after other predictor traits have been considered. We used logistic regression to model the relation between sodium-lithium countertransport and the probability of having hypertension, estimated by the prevalence of hypertension among 172 men and 252 women, aged 47-89 years, from the Caucasian population of Rochester, Minn. When sodium-lithium countertransport was the only predictor trait considered, it made a statistically significant contribution to prediction both in men (model chi(2)1df = 20.50, p < 0.001) and in women (model chi(2)1df = 16.69, p < 0.001). For each standard deviation increase in sodium-lithium counter-transport, the expected odds of having hypertension increased 2.25 times in men (95% confidence interval [CI], 1.44-3.51) and 1.77 times in women (95% CI, 1.32-2.37). When sodium-lithium countertransport was not considered, the other traits identified as predictors were age, body mass index, and plasma apolipoprotein CII and CII squared; plasma apolipoprotein AI was an additional predictor in women but not in men. When sodium-lithium countertransport was added to models that included the other predictors, it improved prediction both in men (increase in model chi(2)1df = 12.29, p < 0.001) and in women (increase in model chi(2)1df = 4.86, p < 0.027). Based on these complete models, when the other predictors remained at their mean values, each standard deviation increase in sodium-lithium countertransport increased the expected odds of having hypertension 2.06 times in men (95% CI, 1.31-3.22) and 1.48 times in women (95% CI, 1.04-2.21). These results establish that sodium-lithium countertransport provides information that is helpful in predicting the probability of having hypertension and is not reflected in other identified predictor traits.


Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.
Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD.


Synergistic hemolysis-inhibition titers associated with caseous lymphadenitis in a slaughterhouse survey of goats and sheep in Northeastern Brazil.
A survey of caseous lymphadenitis was conducted at a goat and sheep slaughterhouse in Northeastern Brazil One hundred and fifty-eight goats and 43 sheep were examined for the presence of abscesses, with bacterial culturing of purulent material to define the etiological agent. Blood was collected simultaneously for determination of serological titer via the synergistic hemolysis-inhibition test which measures antibodies to an exotoxin of Corynebacterium pseudotuberculosis. Thirteen and nine-tenths percent of the goats had abscesses, with a high proportion having mediastinal or pulmonary lesions (9.5%). Two sheep had abscesses, both with internal organ involvement. Corynebacterium pseudotuberculosis was the most frequently isolated organism. Of 22 goats with abscesses, 20 were positive via the synergistic hemolysis-inhibition test. Both of the sheep with abscesses had positive synergistic hemolysis-inhibition titers. The proportion of serological reactors was greater than the proportion of animals with abscesses. The synergistic hemolysis-inhibition test may be detecting subclinically infected animals.


Microencapsulated Cells for Cancer Therapy.
The microencapsulation of different types of cells that are able to produce therapeutic factors is being investigated for the treatment of several human diseases. Most efforts are focused on chronic and degenerative diseases as this strategy could become an alternative to some commonly used parenteral treatments that need to be repeatedly administered. But, this approach has also been investigated in the field of oncology with the aim of providing immunomodulatory antibodies that are able to enhance the patient's inherent immune response against the tumor. These kind of treatments would provide the patient with the therapeutic drug produced in situ, de novo, and in a sustained way, making the therapy more comfortable.Although different devices are nowadays available to produce cell-enclosing alginate-microcapsules, here, we describe the most important steps and advices in order to fabricate alginate-poly-L-lysine-alginate microcapsules containing hybridoma cells for cancer management using an electrostatic bead generator, and how to evaluate the viability of those cells over the time.


Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework.
Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.


Cardiovascular Disease Risk Factor Burden During the Menopause Transition and Late Midlife Subclinical Vascular Disease: Does Race/Ethnicity Matter?
Background The extent to which cardiovascular disease (CVD) risk factors across the menopause explain racial/ethnic differences in subclinical vascular disease in late midlife women is not well documented and was explored in a multi-ethnic cohort. Methods and Results Participants (n=1357; mean age 60 years) free of clinical CVD from the Study of Women's Health Across the Nation had common carotid artery intima-media thickness, interadventitial diameter, and carotid plaque presence assessed by ultrasonography on average 13.7 years after baseline visit. Early to late midlife time-averaged cumulative burden of traditional CVD risk factors calculated using serial measures from baseline to the ultrasound visit were generally less favorable in black and Hispanic women compared with white and Chinese women, including education and smoking status and time-averaged cumulative blood pressure, high-density lipoprotein cholesterol, and fasting insulin. Independent of these risk factors, BMI, and medications, common carotid artery intima-media thickness was thicker in black women, interadventitial diameter was wider in Chinese women, yet plaque presence was lower in black and Hispanic women compared with white women. CVD risk factor associations with subclinical vascular measures did not vary by race/ethnicity except for high-density lipoprotein cholesterol on common carotid artery intima-media thickness; an inverse association between high-density lipoprotein cholesterol and common carotid artery intima-media thickness was observed in Chinese and Hispanic but not in white or black women. Conclusions Race/ethnicity did not particularly moderate the association between traditional CVD risk factors measured across the menopause transition and late midlife subclinical vascular disease. Unmeasured socioeconomic, cultural, and nontraditional biological risk factors likely play a role in racial/ethnic differences in vascular health and merit further exploration.


Inflammatory mechanisms and oxidative stress in Peyronie's disease: therapeutic "rationale" and related emerging treatment strategies.
Peyronie's disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronie's disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed.


Progress towards the broad use of non-peptide synthetic macrocycles in drug discovery.
We discuss progress towards addressing three key questions pertaining to the design of screening libraries of synthetic non-peptidic macrocycles (MCs) for drug discovery: What structural and physicochemical properties of MCs maximize the likelihood of achieving strong and specific binding to protein targets? What features render a protein target suitable for binding MCs, and can this information be used to identify suitable targets for inhibition by MCs? What properties of synthetic MCs confer good pharmaceutical properties, and particularly good aqueous solubility coupled with passive membrane permeability? We additionally discuss how the criteria that define a meaningful MC screening hit are linked to the size of the screening library and the synthetic methodology employed in its preparation.


Presence of acute ischaemic lesions on diffusion-weighted imaging is associated with clinical predictors of early risk of stroke after transient ischaemic attack.
Early risk of stroke after a transient ischaemic attack (TIA) can be reliably predicted with risk scores based on clinical features of the patient and the event, but it is unclear how these features correlate with findings on brain imaging and few studies have investigated this in the subacute phase. Two hundred consecutive patients attending a specialist clinic underwent diffusion-weighted brain imaging (DWI) on the day of the clinic (> or =3 days after a TIA) and the presence of recent lesions (positive DWI) was related to the presence of clinical features associated with a high stroke risk and to 2 validated risk scores (ABCD and California). Thirty-one patients (16%) had positive DWI. Increasing ABCD and California scores were associated with positive DWI (p = 0.02 for both) independent of the delay from TIA to scan. Presence of recent ischaemic lesions on DWI correlates with validated clinical scores for risk of stroke after TIA in patients scanned subacutely. Future prognostic studies of DWI after TIA should adjust for the risk scores to determine the independent predictive value of DWI and hence the likely role of DWI in refinements of the scores.


Bacterial biosensors for rapid and effective monitoring of biodegradation of organic pollutants in wastewater effluents.
Significant amounts of toxic substances which are hazardous to animals, plants, microorganisms, and other living organisms including humans are released annually into aquatic and terrestrial environments, mostly from improper wastewater discharges. Early detection of such pollutants in wastewater effluents and proper monitoring before their final release into the environment is therefore necessary. In this study, two whole-cell bacterial biosensors were constructed by transforming competent cells of Shigella flexneri and Shigella sonnei with pLUX plasmids and evaluated for their potential to monitor wastewater samples undergoing degradation by measuring bioluminescence response using a microplate luminometer. Both bacterial biosensors were found to be extremely sensitive to the wastewater samples, with different patterns, concomitant with those of the COD removals demonstrated at the different days of the degradation. Generally higher bioluminescence values were obtained at the later days of the degradation period compared to the initial values, with up to 571.76% increase in bioluminescence value obtained at day 5 for 0.1% (v/v) effluent concentration. Also, a steady decrease in bioluminescence was observed for the bacterial biosensors with increasing time of exposure to the wastewater effluent for all the sampling days. These biosensor constructs could therefore be applicable to indicate the bioavailability of pollutants in a way that chemical analysis cannot, and for in situ monitoring of biodegradation. This has great potential to offer a risk assessment strategy in predicting the level of bioremediation required during municipal wastewater treatment before their final discharge into the aquatic milieu.


Reputational concerns as a general determinant of group functioning.
To understand a group's (dys)functionality, we propose focusing on its members' concerns for their reputation. The examples of prosocial behavior and information exchange in decision-making groups illustrate that empirical evidence directly or indirectly suggests that reputational concerns play a central role in groups. We argue that our conceptualization fulfills criteria for a good theory: enhancing understanding, abstraction, testability, and applicability.


Merkel cell carcinoma of the head and neck: a single institutional experience.
Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromized Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC.


Emergency Department Attending Physician Variation in Opioid Prescribing in Low Acuity Back Pain.
Despite treatment guidelines suggesting alternatives, as well as evidence of a lack of benefit and evidence of poor long-term outcomes, opioid analgesics are commonly prescribed for back pain from the emergency department (ED). Variability in opioid prescribing suggests a lack of consensus and an opportunity to standardize and improve care. We evaluated the variation in attending emergency physician (EP) opioid prescribing for patients with uncomplicated, low acuity back pain (LABP). This retrospective study evaluated the provider-specific proportion of LABP patients discharged from an urban academic ED over a seven-month period with a prescription for opioids. LABP was strictly defined as (1) back pain chief complaint, (2) discharged from ED with no interventions, and (3) predefined discharge diagnosis of back pain. We excluded providers if they had less than 25 LABP patients in the study period. The primary outcome was the physician-specific proportion of LABP patients discharged with an opioid analgesic prescription. We performed a descriptive analysis and then risk standardized prescribing proportion by adjusting for patient and clinical characteristics using hierarchical logistic regression. During the seven-month study period, 23 EPs treated and discharged at least 25 LABP patients and were included. Eight (34.8%) were female, and six (26.1%) were junior attendings (≤ 5 years after residency graduation). There were 943 LABP patients included in the analysis. Provider-specific proportions ranged from 3.7% to 88.1% (mean 58.4% [SD +/- 22.2]), and we found a 22-fold variation in prescribing proportions. There was a six-fold variation in the adjusted, risk-standardized prescribing proportion with a range from 12.0% to 78.2% [mean 50.4% (SD +/-16.4)]. We found large variability in opioid prescribing practices for LABP that persisted after adjustment for patient and clinical characteristics. Our findings support the need to further standardize and improve adherence to treatment guidelines and evidence suggesting alternatives to opioids.


Self-assembly via branching morphologies in nematic liquid-crystal nanocomposites.
We demonstrate that the morphological diversity in liquid-crystal hybrid systems is much richer than previously anticipated. More importantly, we reveal the existence of a dual mechanism for self-assembly of nanoparticles via morphological instabilities at phase boundaries. Using numerical simulations, we study the growth of isolated nematic droplets in an isotropic liquid crystal (LC) doped with nanoparticles (NPs) and provide insight into the nature of microstructure evolution in LC hybrids. Our work expands the numerically accessible time and length scales in these systems, capturing morphologies which develop under the competition of nonequilibrium elastic interactions, diffusive instabilities mediated by NP transport, and the anisotropy of the nematic field. By mapping nematic morphologies, we also propose a methodology for estimating various important LC material parameters that are difficult to obtain experimentally.


Examination of preventive interventions for families with depression: evidence of change.
Thirty-seven families who had a child between the ages of 8 and 15 (mean age = 12.0 years) and had at least one parent, who had experienced a recent episode of affective disorder were assigned randomly to one of two psychoeducational interventions. The interventions (clinician-facilitated or lecture-group discussion) were designed to prevent childhood depression and related problems through decreasing the impact of related risk factors and encouraging resiliency-promoting behaviors and attitudes. They were similar in content but differed in the level of the children's involvement and the degree to which the families' individual life experiences were linked to the educational material. Assessments included standard diagnostic and social functioning instruments and interviews designed specifically for this project to assess behavior and attitude change. Each parent and child was individually assessed by separate assessors who were blind to information about the other family members. Parent participants in both groups reported being satisfied with the intervention. Clinician group participants reported a significantly larger number of overall changes, as well as higher levels of change regarding communications about the illness with their children and increased understanding by the children of their illness. Significantly more children in the clinician group also reported they gained a better understanding of parental affective illness as a result of their participation in the project.


Diminished Dynamic Physical Performance Is Associated With Orthostatic Hypotension in Geriatric Outpatients.
Orthostatic hypotension (OH), a blood pressure drop after postural change, is a highly prevalent and disabling syndrome in older adults. Yet, the association between physical performance and OH is not clearly established. The aim of this study was to determine whether different types of physical performance are associated with OH in a clinically relevant population of geriatric outpatients. This cross-sectional study included 280 geriatric outpatients (mean age: 82.2 years, standard deviation: 7.1). Orthostatic hypotension was determined using intermittently measured blood pressure and continuously measured blood pressure in a random subgroup of 58 patients. Physical performance was classified into a dynamic type (4-m Walk Test, Chair Stand Test, and Timed Up and Go test) and a static type (standing balance tests, handgrip strength). Associations were analyzed using logistic regression models with adjustments for age, sex, weight, and height. Diminished physical performance on the Chair Stand Test was associated with OH measured intermittently. Diminished physical performance on all dynamic physical domains (4-m Walk Test, Chair Stand Test, and Timed Up and Go test) was associated with OH measured continuously. Static physical performance was not significantly associated with OH. Dynamic physical performance tests with a substantial postural change and center of mass displacement were significantly associated with OH. The influence of physical performance on OH in daily routine activities should be further explored to establish counteracting interventions.


Enhanced mid-latitude tropospheric warming in satellite measurements.
The spatial distribution of tropospheric and stratospheric temperature trends for 1979 to 2005 was examined, based on radiances from satellite-borne microwave sounding units that were processed with state-of-the-art retrieval algorithms. We found that relative to the global-mean trends of the respective layers, both hemispheres have experienced enhanced tropospheric warming and stratospheric cooling in the 15 to 45 degrees latitude belt, which is a pattern indicative of a widening of the tropical circulation and a poleward shift of the tropospheric jet streams and their associated subtropical dry zones. This distinctive spatial pattern in the trends appears to be a robust feature of this 27-year record.


Widespread bidirectional promoters are the major source of cryptic transcripts in yeast.
Pervasive and hidden transcription is widespread in eukaryotes, but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Although CUT degradation mechanisms have been analysed in detail, the genome-wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high-resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3' Long-SAGE (serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 5' end. Our study of glycolysis genes, as well as recent results from the literature, indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short-lived unstable transcripts present at very low steady-state levels.


The angiotensin II pressor system of the rat forebrain.
An anterior hypothalamic knife cut that leaves intact two central sites of action of angiotension II produces the same deficits in the pressor responses to angiotensin II that have been attributed to destruction of two circumventricular organs (the subfornical organ and the organum vasculosum of the lamina terminalis). The central pressor actions of angiotensin II are necessary for the full expression of renin-dependent renal hypertension. The anterior hypothalamic knife cut attenuates renin-dependent aortic ligation hypertension. It has been shown that electrolytic destruction more anterior to this knife cut, in the anteroventral 3rd ventricle region, also attenuates two forms of renin-dependent hypertension, aortic ligation hypertension and two-kidney Goldblatt hypertension in the rat. Electrolytic lesions in the subfornical organ also reduce renin-dependent, two-kidney Goldblatt hypertension. These data are consistent with the hypothesis that a common efferent system from the organum vasculosum of the lamina terminalis and subfornical organ mediates the central pressor response to angiotensin II and is involved in the development of renin-dependent hypertension. A model is proposed for the circuitry in the rat forebrain that is involved in the pressor response to angiotensin II.


Measurement of duty cycles of metal grating masks formed on dielectric substrates.
A nondestructive method for measuring the duty cycles of metal grating masks formed on top of dielectric substrates is proposed. For a near-normal angle of incidence, the zeroth diffracted order transmission efficiency curves for both TE and TM polarized probe lights, as a function of duty cycles, behave linearly in the duty cycle ranging from 0 to 1. By comparing the measured efficiencies, or the ratio of zeroth-order transmission efficiency for TM polarization to that for TE polarization, with that of the rigorous-coupled wave analysis (RCWA) method for a fixed grating period and depth, one can determine the duty cycle of the grating. By selecting the probe light appropriately, the measurement errors originating from deviations of the incident angle and grating depth can be negligible. This method is applicable for all metal gratings, which are not easy to measure nondestructively due to fine grooves smaller than the wavelength. This method is simple, accurate, nondestructive, and low-cost. The results of experimental verification are presented and show excellent agreement with scanning electron microscope images.


Treatment for Acquired Apraxia of Speech: A Systematic Review of Intervention Research Between 2004 and 2012.
The aim was for the appointed committee of the Academy of Neurological Communication Disorders and Sciences to conduct a systematic review of published intervention studies of acquired apraxia of speech (AOS), updating the previous committee's review article from 2006. A systematic search of 11 databases identified 215 articles, with 26 meeting inclusion criteria of (a) stating intention to measure effects of treatment on AOS and (b) data representing treatment effects for at least 1 individual stated to have AOS. All studies involved within-participant experimental designs, with sample sizes of 1 to 44 (median = 1). Confidence in diagnosis was rated high to reasonable in 18 of 26 studies. Most studies (24/26) reported on articulatory-kinematic approaches; 2 applied rhythm/rate control methods. Six studies had sufficient experimental control for Class III rating according to the Clinical Practice Guidelines Process Manual (American Academy of Neurology, 2011), with 15 others satisfying all criteria for Class III except use of independent or objective outcome measurement. The most important global clinical conclusion from this review is that the weight of evidence supports a strong effect for both articulatory-kinematic and rate/rhythm approaches to AOS treatment. The quantity of work, experimental rigor, and reporting of diagnostic criteria continue to improve and strengthen confidence in the corpus of research.


Variable sea-ice conditions influence trophic dynamics in an Arctic community of marine top predators.
Sea-ice coverage is a key abiotic driver of annual environmental conditions in Arctic marine ecosystems and could be a major factor affecting seabird trophic dynamics. Using stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) in eggs of thick-billed murres (Uria lomvia), northern fulmars (Fulmarus glacialis), glaucous gulls (Larus hyperboreus), and black-legged kittiwakes (Rissa tridactyla), we investigated the trophic ecology of prebreeding seabirds nesting at Prince Leopold Island, Nunavut, and its relationship with sea-ice conditions. The seabird community of Prince Leopold Island had a broader isotopic niche during lower sea-ice conditions, thus having a more divergent diet, while the opposite was observed during years with more extensive sea-ice conditions. Species' trophic position was influenced by sea ice; in years of lower sea-ice concentration, gulls and kittiwakes foraged at higher trophic levels while the opposite was observed for murres and fulmars. For murres and fulmars over a longer time series, there was no evidence of the effect of sea-ice concentration on species' isotopic niche. Results suggest a high degree of adaptation in populations of high Arctic species that cope with harsh and unpredictable conditions. Such different responses of the community isotopic niche also show that the effect of variable sea-ice conditions, despite being subtle at the species level, might have larger implications when considering the trophic ecology of the larger seabird community. Species-specific responses in foraging patterns, in particular trophic position in relation to sea ice, are critical to understanding effects of ecosystem change predicted for a changing climate.


Surgical Treatment of Splenic Artery Pseudoaneurysm with Digestive Tract Communication - Presentation of Two Cases.
Splenopancreatectomy performed for pancreatic pseudo-cyst with splenic artery pseudo-aneurysm and communication with the digestive tract (stomach or colon) is a very rare indication and a small number of these procedures are described in literature. Managing peri-pancreatic pseudo-aneurysm is complex and can be challenging. Surgical treatment is of curative intent and can involve multiple visceral resections. Surgery can be performed in an emergency setting, if the patient presents cataclysmic bleeding, or in a planned manner if the pseudo-aneurysm is discovered incidentally or if the patient manages to overcome the initial bleeding. In this paper we present two cases of pancreatic pseudo-cysts with splenic artery pseudo-aneurysms and communication with the digestive tract (one with pseudo-cystic-colonic communication and the other one with gastric communication). Both patients were males, suffered from chronic pancreatitis and were known to have pancreatic pseudo-cysts. For the treatment of the first patient, surgery was performed in an elective setting, after intensive investigations. The other patient presented with cataclysmic bleeding and emergency surgery was performed in order to control the bleeding. We conclude that surgery remains the main option of treatment for these patients. It can be used as a first line of treatment or secondary to endovascular procedures.


Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group.
We conducted a randomized, double-blind, placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release (XR) and fluoxetine in outpatients with major depression and concomitant anxiety. Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were randomly assigned to once-daily venlafaxine XR, fluoxetine, or placebo for 12 weeks. Efficacy was assessed with the Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scale. Among 359 outpatients, venlafaxine XR and fluoxetine were significantly superior (p < .05) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study. Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item. At week 12, the HAM-D response rate was 43% on placebo, 67% on venlafaxine XR, and 62% on fluoxetine (p < .05). The HAM-D remission rate was significantly higher (p < .05) at weeks 3, 4, 6, 8, 12, and final evaluation with venlafaxine XR and at weeks 8, 12, and final evaluation with fluoxetine than with placebo. The HAM-A response rate was significantly higher (p < .05) with venlafaxine XR than with fluoxetine at week 12. The incidence of discontinuation for adverse events was 5% with placebo, 10% with venlafaxine XR, and 7% with fluoxetine. Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine.


National institutes of health stroke scale item profiles as predictor of patient outcome: external validation on independent trial data.
National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort. We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a-NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b-NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles' discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS; using the full distribution and dichotomized, mRS, 0-1) at day 90 and mortality by 90 days. We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c-statistics of a-NIHSS and b-NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70-0.72) and for mortality, 0.74 (0.73-0.75) and 0.75 (0.73-0.76), respectively. Calibration was good. These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score.


Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.


Scientific, societal and pedagogical approaches to tackle the impact of climate change on marine pollution.
Marine pollution impacts coastal nations around the world, and more so: (a) in confined maritime areas with significant marine traffic, (b) where exploitation of natural and mineral resources is taking place, or (c) in regions witnessing pressure from tourism, local population growth, and industry. In this work, Digital Elevation Models, hydrographic, and climatic data are used together with computer simulations to understand the control of climate change on marine pollution. The results show that different climate change signals can potentially alter the flow and concentration of pollution in the European Seas, when compared to the present day. Ultimately, this work identifies the main sources of marine pollution as: (1) rivers and streams near cities and industrialised areas, (2) coastal areas experiencing sudden demographic pressures, (3) offshore shipping lanes in which oil and other marine debris are released, and (4) areas of rugged seafloor where industrial fishing takes place. This paper finishes by describing new educational material prepared to teach school children around the world. It explains why how a new training curriculum and e-game developed by Sea4All can be crucial in future Environmental Education and Education for a Sustainable Development.


The influence of spatiotemporal conditions and personality on survival in reintroductions-evolutionary implications.
Personality exists in non-human animals and can impact fitness. There is, however, a shortage of empirical studies in certain areas within the field, and fundamental evolutionary theory on personality remains largely untested. For example, little is known on how variation in personality is maintained over evolutionary time. Theory suggests that fluctuating selection pressures due to spatiotemporal variation in conditions, e.g. food availability, is a possible mechanism and a few studies have shown that the success of different personality types varies with spatiotemporal conditions. However, it remains unknown whether different mechanisms can maintain personality within a species. Here we use a reintroduction programme for the critically endangered European mink (Mustela lutreola) to test whether multiple personality trait domains (boldness, exploration and sociability) affected survival in two different years and islands. This was done through pre-release personality tests and post-release radio-tracking monitoring. Survival was positively correlated with boldness, whereas the relationship with exploration was either negative or positive depending on year/island. The results show a complex relationship between personality and survival and suggest that exploration can be maintained over evolutionary time via spatiotemporal variation in conditions. However, in contrast to exploration, boldness did not vary spatiotemporally and sociability had no impact on survival. This indicates that different personality trait domains might be maintained by different mechanisms. To date, personality has been studied primarily within behavioural sciences, but through empirical findings we highlight the importance of personality also in ecology and conservation biology.


Effect of Schooling on Age-Disparate Relationships and Number of Sexual Partners Among Young Women in Rural South Africa Enrolled in HPTN 068.
Attending school may have a strong preventative association with sexually transmitted infections among young women, but the mechanism for this relationship is unknown. One hypothesis is that students who attend school practice safer sex with fewer partners, establishing safer sexual networks that make them less exposed to infection. We used longitudinal data from a randomized controlled trial of young women aged 13-20 years in the Bushbuckridge district, South Africa, to determine whether the percentage of school days attended, school dropout, and grade repetition are associated with having a partner 5 or more years older (age-disparate) and with the number of sexual partners in the previous 12 months. Risks of having an age-disparate relationship and number of sexual partners were compared using inverse probability of exposure weighted Poisson regression models. Generalized estimating equations were used to account for repeated measures. Young women who attended fewer school days (<80%) and who dropped out of school were more likely to have an age-disparate relationship (risk difference 9.9%, 95% confidence interval [CI]: 3.9% to 16.0%; risk difference (%) dropout 17.2%, 95% CI: 5.4% to 29.0%) and those who dropped out reported having fewer partners (count difference dropout 0.343, 95% CI: 0.192 to 0.495). Grade repetition was not associated with either behavior. Young women who less frequently attend school or who drop out are more likely to have an age-disparate relationship. Young women who drop out have overall more partners. These behaviors may increase the risk of exposure to HIV infection in young women out of school.


Biodiversity conservation in agricultural landscapes: challenges and opportunities of coffee agroforests in the Western Ghats, India.
The new approaches advocated by the conservation community to integrate conservation and livelihood development now explicitly address landscape mosaics composed of agricultural and forested land rather than only protected areas and largely intact forests. We refer specifically to a call by Harvey et al. (2008) to develop a new approach based on six strategies to integrate biodiversity conservation with sustainable livelihoods in Mesoamerican landscape mosaics. We examined the applicability of this proposal to the coffee agroforests of the Western Ghats, India. Of the six strategies, only one directly addresses livelihood conditions. Their approach has a clear emphasis on conservation and, as currently formulated risks repeating the failures of past integrated conservation and development projects. It fails to place the aspirations of farmers at the core of the agenda. Thus, although we acknowledge and share the broad vision and many of the ideas proposed by this approach, we urge more balanced priority setting by emphasizing people as much as biodiversity through a careful consideration of local livelihood needs and aspirations.